In clinical trials bupropion has been shown to double long-term smoking cessation rates. Nevertheless, most smokers using bupropion relapse back to smoking within the first few weeks of cessation. Bupropion has been hypothesized to help smokers to quit in part by reducing the reinforcing effects of smoking during the typical 1-week pre-quitting treatment phase. Learning theory and previous basic human and animal research support the hypothesis that a longer duration of bupropion treatment prior to the target quit date (TQD) will yield greater decreases in smoking satisfaction and the number of cigarettes smoked per day before quitting, and higher rates of continuous cessation after quitting. The proposed research is the first study of which we are aware to systematically vary the pre-quitting duration of bupropion treatment in smokers to test these predictions. A two group randomized experimental design will be used. One hundred male and female smokers who are motivated to quit smoking will be randomized to a brief run-in group (3 weeks of placebo, followed by the typical 1 week of pre-TQD bupropion) and an extended run-in group (4 weeks of pre-TQD bupropion). Both groups will receive 7 weeks of post-TQD bupropion, as well as group behavioral counseling for smoking cessation. During the pre-quitting treatment phase we predict that bupropion will reduce the number of cigarettes smoked daily and smoking satisfaction, relative to placebo. During a 3-month post-quitting phase, we predict that relapse will be lower in those who experience the greatest pre-quit reductions in smoking rate and satisfaction. We will conduct exploratory analyses of whether cessation is greater for subjects in the extended run-in group compared to the brief run-in group, and whether this effect is mediated by differences in the pre-quit effects of bupropion. This theory-based research may lead to enhanced treatment with bupropion and more broadly stimulate programmatic basic and clinical studies that improve cancer control through a better understanding of learning and behavioral processes implicated in pharmacotherapy for tobacco cessation. [unreadable] [unreadable]